Browsing by Author "Sumit Kumar Hira"

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A 1,8 naphthalimide anchor rhodamine B based FRET probe for ratiometric detection of Cr3+ion in living cells
(Elsevier B.V., 2019) Susanta Adhikari; Sabyasachi Ta; Avijit Ghosh; Subhajit Guria; Abhishek Pal; Manisha Ahir; Arghya Adhikary; Sumit Kumar Hira; Partha Pratim Manna; Debasis Das
A 2-(1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)acetaldehydeanchored rhodamine B based probe, RDNAP detects Cr3+ ion by fluorescence resonance energy transfer (FRET) process in aqueous buffered acetonitrile media (7:3, v/v). Conversely, conjugation of 2-(1,3-dioxo-6-(piperidin-1-yl)-1H-benzo[de]isoquinolin-2(3H)-yl)acetaldehyde with rhodamine B provides another probe, RDNAP-PY that undergoes Cr3+assisted ratiometric fluorescence and colorimetric change in the same media. RDNAP-PY provides higher FRET efficiency and detects as low as 1.81×10−6 M Cr3+with an association constant, 15.9 × 104 M−1. Other common ions do not interfere. RDNAP-PY efficiently images intracellular Cr3+ in live Hep3B, MCF-7, HeLa, SiHa and HEK 293T cells under fluorescence microscope in a ratiometric and time dependent manner. 1H NMR titration and DFT studies strongly support experimental findings. © 2018 Elsevier B.V.
A polynuclear Cu(ii) complex for real time monitoring of mitochondrial cytochrome: C release during cellular apoptosis
(Royal Society of Chemistry, 2020) Somnath Khanra; Sabyasachi Ta; Ankush Paladhi; Milan Ghosh; Subhasis Ghosh; Sumit Kumar Hira; Partha Partim Manna; Paula Brandão; Vítor Félix; Debasis Das
A new amide-imine conjugate, 2-hydroxybenzoic acid-(2-hydroxybenzylidene)-hydrazide (L1), is employed to prepare a single crystal X-ray structurally characterized poly-nuclear Cu(ii) complex (M1). M1 selectively and spatially interacts with cytochrome C (Cyt C) to allow fluorescence imaging of intracellular translocation events in living cells. Thus, direct visualization of a Cyt C translocation event during an apoptotic process is achieved for the first time. The binding constant and LOD are 7.52 × 104 M-1 and 34.0 nM, respectively. © 2020 The Royal Society of Chemistry.
A unique benzimidazole-naphthalene hybrid molecule for independent detection of Zn2+ and N3 − ions: Experimental and theoretical investigations
(Elsevier B.V., 2019) Sabyasachi Ta; Sudipta Das; Milan Ghosh; Mahuya Banerjee; Sumit Kumar Hira; Partha Pratim Manna; Debasis Das
Single crystal X-ray structurally characterized benzimidazole-naphthalene hybrid (NABI) functions as a unique dual analyte sensor that can detect Zn2+ cation and N3 − anion independently. The NABI forms chelate with Zn2+ to inhibit internal charge transfer (ICT) and –CH[dbnd]N– isomerisation resulting chelation enhanced fluorescence (CHEF). On the other hand, the sensing of N3 − is based on formation of supramolecular H-bonded rigid assembly. The association constant of NABI for Zn2+ and N3 − ions are 19 × 104 M−1 and 11 × 102 M−1, respectively. Corresponding limit of detections (LOD) are 6.85 × 10−8 and 1.82 × 10−7 M, respectively. NABI efficiently detects intracellular Zn2+ and N3 − ions with no cytotoxicity on J774A.1cells under fluorescence microscope. DFT studies unlock underlying spectroscopic properties of free NABI and Zn2+/N3 − bound forms. © 2018 Elsevier B.V.
ATP-Decorated Mesoporous Silica for Biomineralization of Calcium Carbonate and P2 Purinergic Receptor-Mediated Antitumor Activity against Aggressive Lymphoma
(American Chemical Society, 2018) Prateek Srivastava; Sumit Kumar Hira; Divesh Narayan Srivastava; Vivek Kumar Singh; Uttam Gupta; Ranjeet Singh; Ram Adhar Singh; Partha Pratim Manna
Adenosine triphosphate (ATP) is an important transmitter that mediates various biological effects via purinergic receptors (P2 receptors) in cancer. We investigated the antitumor activity of ATP-decorated and doxorubicin (DOX)-loaded mesoporous silica with biomineralization of calcium carbonate against a highly aggressive and metastatic murine lymphoma called Dalton's lymphoma (DL). Our results suggest that this nanocomposite has unique effects with respect to the morphology and properties of calcium carbonate on the surface of the nanoparticle. DOX in the nanoparticles was prevented from quick release via the interactions of the phosphate group present on ATP and calcium carbonate. This construct is significantly tumoricidal against parental and DOX-resistant DL cells and is thus a promising candidate for applications in drug delivery. The composite nanomaterial has excellent biocompatibility with higher uptake and acts via the participation of the purinergic receptor P2X7. The nanocomposite induces significantly higher apoptosis in tumor cells compared with DOX alone. Treatment of DL-bearing mice with the construct significantly reduces tumor burden, in addition to augmenting the lifespan of tumor-bearing mice as demonstrated by a sustained healthy life of the animals and improved histopathological parameters. © 2018 American Chemical Society.
Brightening Quinolineimines by Al3+ and Subsequent Quenching by PPi/PA in Aqueous Medium: Synthesis, Crystal Structures, Binding Behavior, Theoretical and Cell Imaging Studies
(American Chemical Society, 2017) Sharad Kumar Asthana; Ajit Kumar; Neeraj; Shweta; Sumit Kumar Hira; Partha Pratim Manna; K.K. Upadhyay
Recent years have witnessed an upsurge of Al3+ selective optical sensors involving simple Schiff bases to other complex organic frameworks. However, more than ∼95% of such reports lack crystallographic evidence, and proposals of binding sites for Al3+ are based upon spectroscopic evidence only. We herein synthesized and fully characterized a quinolineimine derivative (CMO) and explored its potential toward efficient detection of Al3+ with crystallographic evidence. The ongoing nonradiative photoinduced electron transfer (PET) and excited state intramolecular proton transfer (ESIPT) processes in CMO got inhibited via the chelation enhanced fluorescence (CHEF) effects induced by Al3+, and consequently turn-on fluorescence response was observed with 18-fold emission enhancements. The theoretical calculations performed were in good consonance with experimental results. We also explored further the applicability of the CMO·Al3+ complex toward highly sensitive and selective detection of inorganic phosphate (PPi) and an explosive picric acid (PA) via fluorescence quenching processes through two different chemical routes. The bioimaging of Al3+ and PPi were carried out in the living human cancer cells (MCF-7). © 2017 American Chemical Society.
Cellular therapy by allogeneic macrophages against visceral leishmaniasis: Role of TNF-α
(Academic Press Inc., 2014) Partha Pratim Manna; Sumit Kumar Hira; Anirban Basu; Santu Bandyopadhyay
Tumor necrosis factor α (TNF-α) is an essential player in infection with Leishmania, controlling inflammatory lesion and parasite killing. We recently have shown the leishmanicidal activity of transmembrane form of TNF (mTNF) derived from allogeneic natural killer (NK) cells in experimental visceral leishmaniasis. Allogeneic macrophages and human monocytes derived mTNF has significantly higher antileishmanial activity compared to allogeneic NK cells. Unlike NK cells, syngeneic macrophages also possess antileishmanial activity, although degree of activity is significantly less compared to allogeneic macrophages. Cellular therapy by intravenous transfer of allogeneic macrophages enhances leishmanicidal effect against the established infection in susceptible animal by reducing the splenic parasite burden to 28.3±4.71×105 compared to 256.00±17.36×105 in control group. In vivo treatment with anti-mouse TNF-α reduces the therapeutic efficacy of the allogeneic macrophages by increasing the parasite load in spleen of infected mice. These results demonstrated that allogeneic and xenogeneic macrophages induce cytokine mediated protective mechanism against infected macrophages via TNF-α in vitro and, possibly in vivo. The macrophage mediated protective role in absence of T cell help demonstrate an unique property of the mononuclear phagocytes in controlling infection and inflammation in visceral leishmaniasis, despite being acts as a host cell for the same parasite. © 2014 Elsevier Inc.
Detection of Hg 2+ ion using highly selective fluorescent chemosensor in real water sample and in-vitro cell study upon breast adenocarcinoma (MCF-7)
(Taylor and Francis Ltd., 2019) Swapan Dey; Ashish Kumar; Sumit Kumar Hira; Partha Pratim Manna
A novel rhodamine-based chemosensor (R) was designed and synthesised for selective recognition of Hg 2+ ion in real water samples collected from different places. The chemosensor was prepared in green condition with high yield. The selectivity of R was examined with various metal ions, among which only Hg 2+ was identified selectively with off–on mechanism along with enhancement of fluorescence. Metal ions recognition has been carried out using UV–vis and fluorescence studies taking µM concentration of chemosensor R in HEPES buffer. The detection limit of R was calculated and found to be 4.4 × 10 –9 M. Quantum chemical (DFT) calculation was carried out in order to acquire knowledge about the stability of R in presence of Hg 2+ ions. Cell viability and fluorescence microscopic experiments showed R as cytocompatible and can be used as a fluorescent probe for detecting Hg 2+ in living cells. © 2019, © 2019 Informa UK Limited, trading as Taylor & Francis Group.
Development of a PAMAM Dendrimer for Sustained Release of Temozolomide against Experimental Murine Lymphoma: Assessment of Therapeutic Efficacy
(American Chemical Society, 2021) Ugir Hossain Sk; Sumit Kumar Hira; Abhinandan Rej; Debapriya Roymahapatra; Partha Pratim Manna
Enhanced drug localization at the tumor sites with minimal toxicity was demonstrated using dendrimer-conjugated temozolomide for treating experimental lymphoma, developed as a solid tumor. Herein, we have constructed a polyamidoamine (PAMAM) dendrimer conjugated with temozolomide to enhance the stability of the active drug metabolites, derived from the prodrug temozolomide. Our results suggest that the active drug (5-(3-methyltriazen-1-yl)imidazole-4-carboxamide) (MTIC) (derived from temozolomide) showed stable and sustained release from the dendrimer-temozolomide conjugate, suggesting the suitability of the construct for therapy. Besides growth inhibition and direct killing, the dendrimer-temozolomide construct induced extensive apoptosis not only in parental Dalton lymphoma tumor cells but also in the doxorubicin-resistant form of the tumor cells. Dendrimer-temozolomide conjugation significantly reduced the solid tumor growth and increased the lifespan with better prognosis, including improved histopathology of the treated mice, while untreated littermates developed extensive metastasis and succumbed to death. © 2021 American Chemical Society.
Development of a selective reaction-based turn-on fluorosensor and biomarker for hypochlorite ions in aqueous media
(Royal Society of Chemistry, 2019) Ejaj Ahmmed; Somenath Lohar; Sumanta Ghatak; Sumit Kumar Hira; Partha Pratim Manna; Pabitra Chattopadhyay
A new organic moiety, 2-benzotriazol-2-yl-6-[1,3]dithiolan-2-yl-4-ethyl-phenol (LH), was designed, synthesized and structurally characterized as an excellent sensor for hypochlorite ions in aqueous media at pH 7.4. The non-fluorescent LH showed outstanding ICT-based switch-on fluorescence for hypochlorite ions at a concentration as low as 12.58 nM with great sensitivity based on the hypochlorite ion-selective controlled oxidation cleavage reaction of its thioacetal linkage, which was supported by 1HNMR and 13CNMR titrations. The observed spectroscopic changes were validated by theoretical (DFT) calculations. The non-cytotoxic probe has potential application for hypochlorite (ClO-) ion imaging in living cells, which was revealed by imaging human breast cancer (MCF-7) and murine macrophage (J774A1) cell lines via fluorescence microscopy. © 2019 The Royal Society of Chemistry.
Down regulation of CD24 and HER-2/neu in breast carcinoma cells by activated human dendritic cell. Role of STAT3
(2012) Sumit Kumar Hira; Partha Pratim Manna
Human dendritic cells (DCs) stimulated with cytokines and LPS down regulate the expression of proto-oncogene HER-2/neu and GPI linked protein CD24 in breast cancer cell lines. We demonstrated that naïve DC from human peripheral blood, when stimulated with IFN-γ, IL-15 or LPS reduces the expression of HER-2/neu and CD24, via activation of TNF-α. Pretreatment of tumor cells with STAT3 specific inhibitors or knocking down of STAT3 by SiRNA makes the tumor cell more susceptible to apoptosis and DC mediated inhibition of both CD24 and HER-2/neu. Thus DC could acts as an inhibitory regulator in suppressing oncogene and prevention of metastasis. © 2012 Elsevier Inc.
Downregulation of endogenous STAT3 augments tumoricidal activity of interleukin 15 activated dendritic cell against lymphoma and leukemia via TRAIL
(Academic Press Inc., 2014) Sumit Kumar Hira; Indrani Mondal; Debasis Bhattacharya; Partha Pratim Manna
Effector functions in tumor resistance by dendritic cells (DCs) are less well characterized. In this study, we describe that the murine DCs upon stimulation with recombinant IL-15 in vitro or in vivo, expresses TNF superfamily member TRAIL which mediates cytotoxicity and growth inhibition against a murine lymphoma called Dalton lymphoma (DL) via apoptosis. Presence of tumor lysate or intact tumor cells significantly reduces the DC mediated tumoricidal effect, possibly via masking and down-regulating TRAIL in DCs. The antitumor effect of DC derived TRAIL was further augmented by deactivation of STAT3 in tumor cells by cucurbitacin I, which makes it more susceptible to DC derived TRAIL Treatment of tumor cells with cucurbitacin I upregulates TRAIL receptor expression in addition to activation of caspases. Compared to naïve DCs, DCs from tumor bearing mice are significantly impaired in TRAIL expression and consequent antitumor functions against DL which was partially restored by activation with IL-15 or LPS. Priming with recombinant IL-15 prolongs the survival of tumor bearing mice treated with cucurbitacin I. Naïve peripheral blood DCs derived from chronic myeloid leukemia (CML) patients have significant impairment in expression of TRAIL and consequent tumoricidal properties against TRAIL sensitive lymphoma cell lines and primary tumor cells compared to normal control. © 2014 Elsevier Inc.
Downregulation of STAT3 phosphorylation enhances tumoricidal effect of IL-15-activated dendritic cell against doxorubicin-resistant lymphoma and leukemia via TNF-α
(Elsevier Ltd, 2015) Sumit Kumar Hira; Indrani Mondal; Debasis Bhattacharya; Kailash Kumar Gupta; Partha Pratim Manna
Abstract Although disputed by some, increasing evidence suggests that TNF-α synergies with traditional chemotherapeutic drugs to exert a heightened antitumor effect. The present study investigated the antitumor efficacy of recombinant IL-15 in combination with the STAT3 inhibitor cucurbitacin-I in a doxorubicin-resistant murine lymphoma model. The significance of the work is to understand and design effective strategies in doxorubicin resistant lymphomas. TNF-α is downregulated in dendritic cells from mice with Dalton's lymphoma and shows an inverse relationship with disease progression. Doxorubicin-resistant DL cells have elevated levels of Bcl-2 and Mcl-1 and increased phosphorylation of STAT3. These cells are refractory to dendritic cell derived TNF-α. Doxorubicin resistant Dalton's lymphoma is susceptible to dendritic cell derived TNF-α upon stimulation with the STAT3 inhibitor cucurbitacin-I, which downregulates STAT3 and other survival molecules. The combined treatment of low dose of cucurbitacin-I and rIL-15 is ineffective in mice with doxorubicin resistant Dalton's lymphoma, but a similar therapy prolongs the survival of mice transplanted with parental Dalton's lymphoma. Doxorubicin resistant Dalton's lymphoma responds to therapy with high doses of cucurbitacin-I and rIL-15. Dendritic cell derived from mice responded positively to the therapy and regained their tumoricidal properties with respect to growth inhibition and killing of DL tumor cells. Similar to DL, DC derived from CML patients are impaired in TNF-α expression and are unable to restrict the growth of drug-resistant lymphoma and leukemia cells. This combination approach could be used as a new therapeutic strategy for aggressive and highly metastatic doxorubicin resistant lymphoma. © 2015 Elsevier Ltd.
Doxorubicin loaded pH responsive biodegradable ABA-type Amphiphilic PEG-b-aliphatic Polyketal-b-PEG block copolymer for therapy against aggressive murine lymphoma
(Elsevier Inc., 2020) Sumit Kumar Hira; Kheyanath Mitra; Prateek Srivastava; Shikha Singh; Sambhav Vishwakarma; Ranjeet Singh; Biswajit Ray; Partha Pratim Manna
A novel ABA-type polyethylene glycol (PEG)-b-polyketal (PK)-b-PEG block copolymer was synthesized via click reactions between the monoazido-monomethoxy-PEG and dialkyne terminated aliphatic polyketal with no carboxylic/amide linkages. Formation of the novel block copolymer was confirmed by 1H NMR, GPC, TGA, and DSC studies. The formed copolymer has shown faster degradation at acidic pH. Self-assembly of this block copolymer (average size 6.2 nm) was assessed by fluorescence study using pyrene as a probe. Doxorubicin loaded block copolymeric micelles (69.9 nm) have shown pH dependent elevated drug release at pH 6.4, indicating its potential as a pH responsive nano-carrier for anticancer therapy. The nano-sized copolymer demonstrated tumoricidal activities against the lymphoma of murine and human origin with significant levels of growth inhibition and apoptosis. Therapy with doxorubicin loaded copolymer reduced the tumor size and augmented the life span of the tumor bearing animals with improved histopathological parameters, compared with the untreated control. © 2019 Elsevier Inc.
Enhanced bioactivity, biocompatibility and mechanical behavior of strontium substituted bioactive glasses
(Elsevier Ltd, 2016) Sampath Kumar Arepalli; Himanshu Tripathi; Sumit Kumar Hira; Partha Pratim Manna; Ram Pyare; S.P.Singh
Strontium contained biomaterials have been reported as a potential bioactive material for bone regeneration, as it reduces bone resorption and stimulates bone formation. In the present investigation, the bioactive glasses were designed to partially substitute SrO for SiO2 in Na2O–CaO–SrO–P2O5–SiO2 system. This work demonstrates that the substitution of SrO for SiO2 has got significant benefit than substitution for CaO in the bioactive glass. Bioactivity was assessed by the immersion of the samples in simulated body fluid for different intervals. The formation of hydroxy carbonate apatite layer was identified by X-ray diffractometry, scanning electron microscopy (SEM) and energy dispersive spectroscopy. The elastic modulus of the bioactive glasses was measured and found to increase with increasing SrO for SiO2. The blood compatibility of the samples was evaluated. In vitro cell culture studies of the samples were performed using human osteosarcoma U2-OS cell lines and found a significant improvement in cell viability and proliferation. The investigation showed enhancement in bioactivity, mechanical and biological properties of the strontia substituted for silica in glasses. Thus, these bioactive glasses would be highly potential for bone regeneration. © 2016
Essential role of TNF-α in gamma c cytokine aided crosstalk between dendritic cells and natural killer cells in experimental murine lymphoma
(Elsevier B.V., 2020) Uttam Gupta; Sumit Kumar Hira; Ranjeet Singh; Ankush Paladhi; Prateek Srivastava; Partha Pratim Manna
Cooperative and cognitive interaction between the dendritic cells and natural killer cells was investigated for demonstrating the anti-tumor activity against an aggressive murine lymphoma, treated with doxorubicin. Crosstalk between the dendritic cells and the natural killer cells significantly reduced the proliferation of Dalton's lymphoma cells in a dose dependent manner. Treatment of Dalton's lymphoma cells with doxorubicin in vitro enhances the effects of crosstalk against the target cells. This crosstalk between the cells was regulated via stimulation with recombinant interleukin-15, and release of TNF-α which is critically important for the tumoricidal effects. Dendritic cells and the natural killer cells crosstalk activate both the cells and upregulate the expression of CD40, CD69 and CD86 on the dendritic cells. These findings provided new insight regarding these interactions and define a mechanism by which cellular immune response promotes tumoricidal activity against lymphoma in therapeutic setting. © 2019 Elsevier B.V.
Evaluation of carbofuran-mediated toxicity against human lymphocytes and red blood cells in simulated wastewater degraded by coagulation–flocculation
(Springer Verlag, 2017) Roli Saini; Pradeep Kumar; Sumit Kumar Hira; Partha Pratim Manna
Coagulation–flocculation in water treatment has been relied upon aluminum (Al) and iron (Fe) salts for treatment of contaminants present in source waters containing dissolved organic compounds. However, water quality deteriorates day by day which makes it urgent to improve the standards of the treatment procedure. Coagulation–flocculation–sedimentation performance of ferric chloride and alum was comparatively investigated for carbofuran treatment in simulated wastewater. Coagulation trails were performed in a jar test at several pH levels and coagulant doses to determine reduction efficiencies of carbofuran degradation and chemical oxygen demand (COD). Effect of carbofuran on proliferation, viability, and direct cytotoxicity was performed using human neuroblastoma cells U-87. Direct toxicity of carbofuran on human mononuclear cells and red blood cells (RBC) was also analyzed. Carbofuran and its derivatives were found to be relatively safe at low concentration (2–5 μM). However, at slightly higher concentration (8 μM), a moderate loss in viability and proliferative potential was observed. Taken together, these results suggest that carbofuran appears to be safe at moderate or low concentration with respect to viability of normal human lymphocytes and RBC. © 2017, Springer-Verlag Berlin Heidelberg.
Exploring Anticancer and (Bio)catalytic Activities of New Oxovanadium(V), Dioxomolybdenum(VI), and Copper(II) Complexes of Amide-Imine Conjugates
(American Chemical Society, 2019) Sabyasachi Ta; Milan Ghosh; Kajari Ghosh; Paula Brandaõ; Vítor Félix; Sumit Kumar Hira; Partha Pratim Manna; Debasis Das
An amide-imine conjugate, (E)-N′-((2-hydroxynaphthalen-1-yl) methylene)-4-methylbenzohydrazide (PTANAP), derived from 4-methyl-benzoic acid hydrazide (PTA) and 2-hydroxynapthaldehyde, is explored to prepare dinuclear oxovanadium(V), mononuclear dioxomolydenum(VI), and Cu(II) complexes. Single crystal X-ray structurally characterized complexes have been exploited as catalyst for oxidation of ethylbenzene, catechol, and o-aminophenol. The anticancer properties of the oxo-vanadium complex have been explored against human leukemia cell (K-562) and mouse lymphoma cells (2PK3). © 2019 American Chemical Society.
Galunisertib Drives Treg Fragility and Promotes Dendritic Cell-Mediated Immunity against Experimental Lymphoma
(Elsevier Inc., 2020) Sumit Kumar Hira; Abhinandan Rej; Ankush Paladhi; Ranjeet Singh; Jayasree Saha; Indrani Mondal; Sankar Bhattacharyya; Partha Pratim Manna
Immunology; Immunity; Cancer © 2020 The Authors; Galunisertib (LY2157299) is a selective ATP-mimetic inhibitor of TGF-β receptor-I activation, currently under clinical trial in a variety of cancers. We have tested the combined effects of galunisertib- and interleukin-15-activated dendritic cells in an aggressive and highly metastatic murine lymphoma. Based on the tumor-draining lymph node architecture, and its histology, the combination therapy results in better prognosis, including disappearance of the disease-exacerbating regulatory T cells. Our data suggest that galunisertib significantly enhances the success of immunotherapy with IL-15-activated dendritic cells by limiting the regulatory T cells generation with consequent downregulation of regulatory T cells in the tumor-draining lymph nodes and vascularized organ like spleen. This is also associated with consistent loss p-SMAD2 and downregulation of Neuropilin-1, leading to better prognosis and positive outcome. These results connect the role of combined therapy with the consequent elimination of disease-exacerbating T regulatory cells in a metastatic murine lymphoma. © 2020 The Authors
IL-15 activated human peripheral blood dendritic cell kill allogeneic and xenogeneic endothelial cells via apoptosis
(2013) Partha Pratim Manna; Sumit Kumar Hira; Apabrita Ayan Das; Santu Bandyopadhyay; Kailash Kumar Gupta
IL-15 is a pleotropic cytokine, which plays an important role in natural killer (NK) cell activity, T cell proliferation, and T cell cytotoxic activity. Dendritic cells (DCs) are the major antigen presenting cells in the immune system and presumed to play an important role in immune recognition of allo and xenotransplantation. We showed that IL-15 activated human peripheral blood DC is cytotoxic to human and porcine aortic endothelial cells. Unlike DCs, CD14+ monocytes show no cytotoxicity against the endothelial cells. This cytotoxic potential of IL-15 activated DC against endothelial cells is dose dependent and increases significantly upon treatment of endothelial cells with inflammatory cytokines like TNF-α or IFN-γ. The cytotoxic potential of IL-15 activated DC is associated with apoptosis of endothelial cells, as indicated by the increased Annexin V staining, caspase activation and loss of mitochondrial membrane potential. Further it was observed that DC mediated cytotoxicity against endothelial cell is mediated via granzyme B possibly secreted by the activated DCs. © 2012 Elsevier Ltd.
Immunoinformatics based design and prediction of proteome-wide killer cell epitopes of Leishmania donovani: Potential application in vaccine development
(Taylor and Francis Ltd., 2022) Mohammad Kashif; Sumit Kumar Hira; Partha Pratim Manna
Despite several extensive and exhaustive efforts, search for potential therapy against leishmaniasis has not made much progress. In the present work, we have employed mining strategy to screen Leishmania donovani proteome for identification of promising vaccine candidate. We have screened 21 potential antigenic proteins from 7960 total protein of L. donovani, based on the presence of signal peptide, GPI anchor, antigenicity prediction and substractive proteomic approach. Secondly, we have also performed comprehensive immunogenic epitope prediction from the screened 21 proteins, using IEDB-AR tools. Out of the 21 antigenic proteins, we obtained 11 immunogenic epitopes from 9 proteins. The final results revealed that four predicted epitopes namely; YPAFAALVF, VAVAATVAY, AAAPTEAAL and MYPLVAVVF, have significantly better binding potential with respective alleles and could elicits immune responses. Docking analysis using PATCHDOCK server and molecular dynamic simulation using GROMACS revealed the potential of the sequences as immunogenic epitopes. In silico studies also suggested that the epitopes occupied almost same binding cleft with the respective alleles, when compared with the reference peptides. It is also suggested from the molecular dynamic simulation data that the peptides were intact in the pocket for longer periods of time. Our study was designed to select MHC class I restricted epitopes for the activation of CD8 T cells using immunoinformatics for the prediction of probable vaccine candidate against L. donovani parasites. Communicated by Ramaswamy H. Sarma. © 2021 Informa UK Limited, trading as Taylor & Francis Group.